Last year we reported the results of autoradiographic studies in primates studied with the tracer 1251-5-iodo-6-nitroquipazine (inquip) simultaneously with the 1231-labeled compound, so that in vivo and ex vivo imaging could be performed for comparison. These studies revealed that the uptake of the tracer autoradiographically conformed to the known distribution of serotonin reuptake sites and with the images obtained in vivo using SPECT. We are now in the process of extending these observations to animals which have been pretreated with the serotonergic neurotoxin MDMA. In these studies, we treated rhesus macaques with 5 mg/kg i.V. MDMA twice daily for 4 days two weeks prior to the spect experiments. Because our previous work has demonstrated a half life of nonspecific binding of about 3 hours, animals were studied approximately 17 hours after the tracer injection. Three animals were controls, and three received MDMA injections. One of the mdma pretreated animals was coinjected with the 1251-labeled tracer, and sacrificed for autoradiography following spect imaging as described above. The other two animals were imaged only with the 1231-labeled tracer using spect. Results from the autoradiograms revealed a decrease in tracer binding in the MDMA treated animal which ranged from 40-60%, affecting most brain regions. The spect images also showed reductions in ratios of regional uptake normalized to the uptake in the whole brain. Although the results approached statistical significance despite the small group size (3 animals/group), with 0.05<P<0.10 for thalamus, temporal, and prefrontal cortex. At the present time, these results are preliminary, and are currently being prepared for publication.